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-Adrenoceptor constrictor responses and their modulation in slow-twitch and fast-twitch mouse skeletal muscle
1 Department of Internal Medicine, Hypertension Division, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
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Abstract |
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1- and 2-adrenoceptors mediate these vascular responses in fast-twitch muscle, while their roles in slow-twitch muscle are less well defined. In this study, the phosphorylation of smooth muscle myosin regulatory light chain (smRLC) was measured as an index of vasoconstriction in slow-twitch soleus muscles and fast-twitch extensor digitorum longus (EDL) muscles isolated from C57BL/6J mice. In soleus muscles, incubation with phenylephrine (PE) or UK 14,304 to selectively activate 1- or 2-adrenoceptors resulted in concentration-dependent increases in smRLC phosphorylation. To evaluate metabolic modulation of these responses, vasodilator pathways previously implicated in such modulation in fast-twitch muscle were activated in soleus muscles by treatment with the nitric oxide (NO) donor nitroprusside or the ATP-sensitive potassium (KATP) channel opener cromakalim. Both drugs inhibited responses to UK 14,304, but not to PE. The effect of nitroprusside to antagonize UK 14,304 responses was prevented by inhibition of guanylyl cyclase or by blockade of KATP channels, but not by blockade of other potassium channels. Results were similar in EDL muscles. These data provide the first evidence for 2-adrenoceptor-mediated constriction in slow-twitch muscle, and show that it is sensitive to modulation by NO via a cGMP-dependent mechanism that requires KATP channel activation. Based on the similar findings in soleus and EDL muscles, fibre type does not appear to determine the innate vascular response to 1- or 2-adrenoceptor activation.
(Received 7 December 2004;
accepted after revision 23 December 2004;
first published online 23 December 2004)
Corresponding author G. D. Thomas: University of Texas Southwestern Medical Center, Hypertension Division, 5323 Harry Hines Blvd, Dallas, TX 75390-8586, USA. Email: gail.thomas{at}utsouthwestern.edu
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Introduction |
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1- and 2-adrenoceptor subtypes (Marshall, 1982; Ohyanagi et al. 1991; Dinenno et al. 2002). Animal studies suggest that these receptors play distinct functional roles in the muscle microcirculation, with the 1-adrenoceptors mainly controlling the large resistance arterioles, and the 2-adrenoceptors controlling the small precapillary arterioles (Faber, 1988; Ohyanagi et al. 1991). The 2-adrenoceptors therefore may be optimally positioned to regulate capillary perfusion and distribute intramuscular blood flow according to the metabolic needs of the skeletal muscle cells.
In this regard, vasoconstriction mediated by 2-adrenoceptors appears to be particularly sensitive to inhibition by metabolic disturbances provoked, for example, by muscle hypoxia, ischaemia, or contraction (Anderson & Faber, 1991; McGillivray-Anderson & Faber, 1991; Thomas et al. 1994; Tateishi & Faber, 1995b; Buckwalter et al. 2001; Wray et al. 2004). We and others have reported that the blunted -adrenergic vasoconstriction observed in these conditions is mediated in part by the activation of vasodilatory pathways involving either nitric oxide (NO) or the hyperpolarizing, metabolically regulated ATP-sensitive potassium (KATP) channels (Ohyanagi et al. 1992; Tateishi & Faber, 1995a; Thomas et al. 1997; Thomas & Victor, 1998; Buckwalter et al. 2004; Keller et al. 2004). A mechanistic link between these signalling pathways has been shown in studies of large conduit arteries in which NO and its downstream effector cGMP can activate KATP channels (Murphy & Brayden, 1995; Wu et al. 1999), although it is not clear if a similar interaction also occurs in the muscle microcirculation.
In contrast to the extensive characterization of -adrenoceptor-mediated vasoconstriction and its modulation in fast-twitch muscle, relatively little is known about these responses in slow-twitch muscle. The limited data that have been reported suggest that -adrenergic control of blood flow may differ substantially in muscles with different fibre type profiles. For example, the vasoconstrictor responses to sympathetic nerve activation are reduced in slow-twitch muscles compared to fast-twitch muscles at rest (Folkow & Halicka, 1968; Hilton et al. 1970; Gray, 1971), and may be less susceptible to attenuation in slow-twitch muscles than in fast-twitch muscles during contraction (Thomas et al. 1994). The reasons for these differential responses in slow-twitch and fast-twitch muscles are not known, but could potentially be mediated by differences in the vasoconstrictor responses evoked by either 1- or 2-adrenoceptors, and/or by differences in the susceptibility of these vasoconstrictor responses to metabolic modulation. In particular, a large gap in our understanding of vascular regulation in slow twitch muscle stems from the current lack of information about the role of the 2-adrenoceptors.
Therefore, our primary goal in this study was to evaluate 1- and 2-adrenoceptor-mediated vasoconstrictor responses and their modulation in the microcirculation of muscles composed predominantly of slow-twitch or fast-twitch fibres. To avoid the potentially confounding effects of differences in basal blood flow or sympathetic neural tone in muscles with different fibre type profiles, we performed ex vivo studies using slow-twitch soleus muscles and fast-twitch extensor digitorum longus (EDL) muscles isolated from the mouse hindlimb. To evaluate in situ microvascular responses to direct activation of 1- or 2-adrenoceptors, we measured the phosphorylation of smooth muscle myosin regulatory light chain (smRLC), which is a key biochemical event mediating the activation of myosin ATPase and smooth muscle contraction (Kamm & Stull, 1985; Stull et al. 1991; Somlyo & Somlyo, 1994). Finally, to evaluate the susceptibility of -adrenoceptor responses to metabolic modulation, we exposed muscles to an NO donor or KATP channel agonist to activate specific vasodilator pathways that have previously been implicated in such modulation.
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Methods |
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Experimental protocol
Male and female C57BL/6J mice (The Jackson Laboratory) aged 12–16 weeks were killed with sodium pentobarbital (250 mg kg–1, I.P.). The EDL (mass, 7–14 mg) and soleus (mass, 8–16 mg) muscles were isolated and removed from each hindlimb. Each muscle was secured at one end to an isometric force transducer and at the other end to a fixed support in a tissue bath containing oxygenated (95% O2–5% CO2) physiological saline solution (PSS; pH 7.6, 30°C) composed of (mM) 120.5 NaCl, 4.8 KCl, 1.2 MgSO4, 20.4 NaHCO3, 1.6 CaCl2, 1.2 NaH2PO4, 10 glucose and 1 pyruvate. Muscle tension was adjusted to maintain 1 g of resting tension. Muscles were equilibrated for 30–45 min prior to any drug treatment.
Muscles were treated for 60 s with the 1-adrenoceptor agonist phenylephrine (PE, 1 or 10 µM) or the 2-adrenoceptor agonist UK 14,304 (2 or 20 µM). Preliminary experiments indicated that a 60 s exposure produced maximal smRLC phosphorylation (data not shown). In some experiments, the NO donor sodium nitroprusside (10 nM) or the KATP channel opener cromakalim (7 µM) were added during the last 30 s of the -adrenoceptor agonist exposure. In other experiments, muscles were pretreated for 20 min with antagonists to KATP channels (glibenclamide, 10 µM), voltage-dependent K+ channels (Kv; 4-aminopyridine, 5 mM), large conductance Ca2+-activated K+ channels (KCa; iberiotoxin, 100 nM), small conductance KCa channels (apamin, 100 nM), or soluble guanylyl cyclase (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, ODQ; 50 µM). Drug concentrations were based on previously published data (Ohyanagi et al. 1992; Tateishi & Faber, 1995a) and preliminary experiments from our laboratory. Drugs were added directly to the tissue baths to achieve the given final concentrations. At the end of each experiment, muscles were snap-frozen by tongs prechilled in liquid nitrogen and stored at –80°C for subsequent analysis.
Measurement of smRLC phosphate content
Measurements were performed as previously described (Persechini et al. 1986; Grange et al. 2001). Briefly, frozen muscles were weighed and then homogenized in 500 µl ice-cold 10% trichloroacetic acid (TCA)–acetone solution containing 1 mM dithiothreitol (DTT). After centrifugation at 735 g for 2 min, pellets were washed three times with 500 µl ethyl ether, air-dried for 20 min, and resuspended in 300 µl of an 8 M urea sample buffer containing (mM): 18.5 Tris, 20.4 glycine, 9.2 DTT, and 4.6 EDTA, pH 8.6. Samples were saturated with urea crystals and shaken for 1 h at room temperature to ensure complete protein solubilization.
Extraction of smRLC was performed by adding ice-cold 95% ethanol drop-wise to 25% of the final volume. Samples were incubated on ice for 20 min and centrifuged at 4000 g for 7 min. An equal volume of 20% TCA–2 mM DTT–water was added to the supernatant fraction and samples were incubated on ice for 20 min. After centrifugation at 4000 g for 10 min, pellets were resuspended in 100 µl of 8 M urea sample buffer (minus Tris, plus saturated sucrose and 0.004% bromophenol blue). Samples were solubilized by saturation with urea crystals and pH was maintained by adding 2.5 M Tris base (pH 11.0). Samples were shaken vigorously for 1 h at room temperature and stored at –80°C.
Samples (20 µl) were loaded onto a 10% polyacrylamide gel and electrophoresed at 400 V for 60 min using a running buffer of 214 mM Tris and 266 mM glycine and an identical cathode buffer supplemented with 2 mM thioglycolate and 2 mM DTT. Proteins were transferred to polyvinylidene fluoride (PVDF) membranes (Millipore) at 25 V for 60 min. Membranes were washed briefly in 100% methanol, air-dried for 
20 min, and fixed in 0.4% gluteraldehyde for 30 min. Membranes were then blocked in 5% Amersham Liquid Block for 60 min at room temperature, and incubated overnight at 4°C with a primary monoclonal antibody (ascites diluted 1: 10 000; provided by Kathy Trybus, University of Vermont, Burlington, VT) in 0.5% Amersham Block–PBS that recognizes smooth muscle, but not skeletal muscle, myosin RLC (Lau et al. 1998). Membranes were washed and incubated for 60 min at room temperature with goat antimouse IgG(H + l) conjugated with alkaline phosphatase (1: 10 000; Southern Biotechnology Associates). Phosphorylated and non-phosphorylated smRLC bands were visualized by chemiluminescence (CSPD substrate and Sapphire enhancer, Tropix) according to the manufacturer's instructions. The ratio of phosphorylated smRLC to total smRLC was determined by densitometry (Molecular Analyst, Bio-Rad) and reported as moles Pi per mole of smRLC.
Chemicals
UK 14,304 and glibenclamide were purchased from Research Biochemicals International. All other chemicals were purchased from Sigma. Stock solutions of phenylephrine, nitroprusside, prazosin, yohimbine, 4-aminopyridine, iberiotoxin and apamin were dissolved in dH2O. Stock solutions of UK 14,304, cromakalim, glibenclamide and ODQ were dissolved in 40% DMSO. Final tissue bath concentrations of DMSO were less than 0.1%.
Statistical analysis
Differences in smRLC phosphate content among treatments were analysed using a one-way ANOVA and Scheffé's post hoc tests. P values < 0.05 were considered statistically significant. Data are expressed as means ± S.E.M.
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Results |
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2- or 1-adrenoceptors increases smRLC phosphorylation in soleus and EDL
To evaluate vasoconstrictor responses to -adrenoceptor activation, the ratio of phosphorylated smRLC to total smRLC was measured in extracts of mouse soleus and EDL muscles as illustrated in Fig. 1. As shown in Fig. 2, treating muscles for 60 s with the 2-adrenoceptor agonist UK 14,304 elicited concentration-dependent increases in smRLC phosphorylation. The ratio of phosphorylated smRLC to total smRLC increased from a basal level of 0.16 ± 0.03 in soleus muscles to a maximum of 0.47 ± 0.03, and from 0.15 ± 0.03 in EDL muscles to a maximum of 0.41 ± 0.05. Likewise, treatment with the 1-adrenoceptor agonist phenylephrine increased smRLC phosphorylation from 0.11 ± 0.03 in soleus muscles to a maximum of 0.45 ± 0.06, and from 0.13 ± 0.03 in EDL muscles to a maximum of 0.43 ± 0.12. In preliminary experiments, responses to UK 14,304 or phenylephrine were prevented by pretreatment with the 2-adrenoceptor antagonist yohimbine or the 1-adrenoceptor antagonist prazosin, respectively (data not shown).
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2-adrenoceptor-mediated smRLC phosphorylation by nitroprusside or cromakalim in soleus and EDLA concentration of nitroprusside (10 nM) that would be expected to yield NO in the low physiological range had no significant effect on basal phosphorylation of smRLC in soleus or EDL muscles (Fig. 3). Nitroprusside inhibited the increases in smRLC phosphorylation in response to 20 µM UK 14,304 in both soleus and EDL muscles, but it had no effect on the increases in smRLC phosphorylation induced by 10 µM phenylephrine in either type of muscle. The inhibitory effect of nitroprusside on UK 14,304-mediated smRLC phosphorylation was prevented by treating muscles with ODQ, an inhibitor of soluble guanylyl cyclase (Fig. 3).
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2-adrenoceptor-mediated smRLC phosphorylation requires KATP channels, but not Kv or KCa channelsIncreases in smRLC phosphorylation in response to UK 14,304 were not affected by pretreatment of soleus or EDL muscles with glibenclamide (Fig. 5). As expected, glibenclamide prevented the inhibitory effect of cromakalim on UK 14,304-induced increases in smRLC phosphorylation. Glibenclamide also prevented the inhibitory effect of nitroprusside on UK 14,304-induced increases in smRLC phosphorylation (Fig. 5).
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Discussion |
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-adrenergic control of the microcirculation has been fairly well characterized in fast-twitch muscle (Faber, 1988; Anderson & Faber, 1991; McGillivray-Anderson & Faber, 1991; Ohyanagi et al. 1991, 1992; Tateishi & Faber, 1995a,b), much less is known about such regulation in slow-twitch muscle. In this study, we were particularly interested in probing the role of 2-adrenoceptors, which had not previously been examined in slow-twitch muscle. Using changes in smooth muscle myosin phosphorylation to evaluate in situ vascular responses in mouse hindlimb muscles, we now provide novel functional evidence for 2-adrenoceptors in the microcirculation of slow-twitch muscle. We also show that the vascular responses mediated by these receptors are sensitive to inhibition by a low physiological concentration of NO acting selectively via KATP channels, demonstrating the potential for metabolic modulation of 2-adrenergic vasoconstriction in slow-twitch muscle.
Our finding that the increases in smRLC phosphorylation evoked by either the 2-adrenoceptor agonist UK 14,304 or the 1-adrenoceptor agonist phenylephrine were similar in soleus and EDL muscles suggests that fibre type composition is not a principal determinant of the vascular response to -adrenoceptor activation. In a recent in vitro study of second-order resistance arterioles isolated from rat skeletal muscles with varying proportions of fast-twitch and slow-twitch fibres, Aaker & Laughlin reached the same conclusion regarding 1-adrenergic vasoconstriction (Aaker & Laughlin, 2002). However, in that study 2-adrenergic vasoconstriction could not be evaluated as the vessels did not respond to UK 14,304, either because 2-adrenoceptors are of less functional importance in the control of the large second-order arterioles (Faber, 1988) or because their sensitivity is selectively reduced after in vitro isolation (Ikeoka & Faber, 1993). An advantage of our experimental preparation is that the muscle microvascular network remained intact in its native environment and we were therefore able to observe 2-adrenoceptor responses. It remains to be seen if the spatial distribution of the -adrenoceptors in the microcirculation of slow-twitch muscle is the same as that of fast-twitch muscle, where both 1- and 2-adrenoceptors control the large proximal arterioles and large venules, while the 2-adrenoceptors control the small distal arterioles (Faber, 1988).
The outcome of these ex vivo studies indicating a lack of association between -adrenergic vasoconstrictor responses and muscle fibre type composition would appear to conflict with previous in vivo studies in which sympathetic vasoconstrictor responses were blunted in quiescent slow-twitch versus fast-twitch muscles (Folkow & Halicka, 1968; Hilton et al. 1970; Gray, 1971). Based on our data, we suggest that the results of the in vivo studies cannot be explained by a reduced intrinsic efficacy of either 1- or 2-adrenoceptors in slow-twitch muscle. Other factors that might contribute to this differential sympathetic responsiveness in slow-twitch and fast-twitch muscles but have yet to be explored include variations in sympathetic innervation or in -adrenoceptor densities or reserves.
Another important aspect of our study was to evaluate the sensitivity of -adrenoceptor-mediated constrictor responses to metabolic modulation in muscles with different fibre type compositions. To do so, we used drugs to directly activate specific vasodilator pathways that have been implicated in the metabolic attenuation of -adrenergic vasoconstriction during hypoxia or muscle contraction. This ensured that soleus and EDL muscles were exposed to equivalent vasodilator species and concentrations, which would not have been the case if hypoxia or muscle contraction had been used to stimulate the production of endogenous vasodilator substances given the dissimilar metabolic profiles of slow-twitch and fast-twitch muscles.
Using this strategy, we found that the increase in smRLC phosphorylation in response to 2-, but not 1-, adrenoceptor activation was highly susceptible to modulation by the NO donor nitroprusside and the KATP channel opener cromakalim in soleus muscle. These results provided the first evidence that 2-adrenergic vasoconstriction in slow-twitch muscle is potentially subject to metabolic modulation. Similar results were obtained for the EDL muscle, suggesting that fibre type composition does not influence the intrinsic sensitivity of -adrenergic vasoconstriction to such modulation. These results also confirm at the biochemical level previous studies showing metabolic inhibition of 2-adrenergic vasoconstriction in fast-twitch or mixed skeletal muscles using conventional measurements of blood flow or blood vessel diameter (Anderson & Faber, 1991; McGillivray-Anderson & Faber, 1991; Ohyanagi et al. 1992; Thomas et al. 1994; Tateishi & Faber, 1995a,b; Buckwalter et al. 2001; Rosenmeier et al. 2003; Wray et al. 2004).
These new data would appear to differ from the results of our previous in vivo study in which we reported that sympathetic vasoconstriction was attenuated in the rat hindlimb during contractions of the fast-twitch gastrocnemius, but not slow-twitch soleus, muscles (Thomas et al. 1994). In the present study, the effects of well-defined, uniform vasoconstrictor (-adrenoceptor agonists) and vasodilator (NO, KATP channels) stimuli were evaluated in individual muscles. In contrast, in the previous study, the effects of relatively less specific constrictor (sympathetic nerve stimulation) and dilator (muscle contraction) stimuli were evaluated in the intact hindlimb. Having identified a specific set of conditions in which 2-adrenergic vasoconstriction can be modulated in the isolated soleus muscle, a future challenge is to determine if the findings from this reductionist ex vivo preparation are applicable to vascular regulation in slow-twitch muscles in vivo.
Use of this reductionist preparation also allowed us to probe the mechanism by which NO attenuates 2-adrenergic vasoconstriction in the skeletal muscle microcirculation. In previous in vivo studies in rats, we reported that the effect of hindlimb contraction to attenuate sympathetic vasoconstriction was equally impaired by solo or combined inhibition of NO synthase activity or KATP channel activity (Thomas et al. 1997; Thomas & Victor, 1998). Although those data suggested a potential interaction between NO and KATP channels, we could not definitively exclude a role for other K channels because of concerns about the specificity of the high systemic dose of the KATP channel blocker used in that study. In the present study, we overcame that limitation by using selective concentrations of inhibitors of the major classes of K channels that have been implicated in vascular control. These new data show that the effect of the NO donor nitroprusside to antagonize 2-adrenergic vasoconstriction was mediated specifically by activation of KATP channels, but not by Kv or KCa channels. This interaction might involve cGMP-mediated activation of the KATP channel, as has been reported in earlier studies using conduit blood vessels (Murphy & Brayden, 1995; Wu et al. 1999).
In contrast to the results of our study, nitroprusside has previously been shown to attenuate 1-adrenoceptor-mediated increases in smRLC phosphorylation in the fast-twitch EDL muscle (Grange et al. 2001). These disparate findings are probably due to the 1000-fold difference in the concentration of nitroprusside used in these studies (10 nM
versus 10 µM), and most likely reflect concentration-dependent effects of NO to activate multiple cellular signalling pathways leading to vasorelaxation. In addition to activating KATP channels (Murphy & Brayden, 1995; Wu et al. 1999), NO is reported to activate KCa channels (Robertson et al. 1993; Bolotina et al. 1994), reduce Ca2+ influx (Blatter & Wier, 1994), reduce the Ca2+ sensitivity of the contractile proteins (Sauzeau et al. 2000), and enhance cytosolic removal of Ca2+ by Ca2+-ATPase (Cornwell et al. 1991).
In general, our data indicate that smRLC phosphorylation is a sensitive biological endpoint that can be used to study -adrenergic regulation of the muscle microcirculation. Because smRLC phosphorylation reflects the activity of both myosin light chain kinase (MLCK) and phosphatase (MLCP) (Kamm & Stull, 1985; Kimura et al. 1996; Pfitzer, 2001; Somlyo & Somlyo, 2003), additional studies are needed to determine how the vasoconstrictor and vasodilator stimuli used in our study interact with these regulatory pathways. For example, ligand binding to -adrenoceptors increases cytosolic Ca2+ (Guimaraes & Moura, 2001) which activates the Ca2+–calmodulin-dependent MLCK (Kamm & Stull, 1985), while NO and KATP channels have the opposite effect of reducing cytosolic Ca2+ (Brayden, 2002; Schlossmann et al. 2003) which inhibits MLCK. Furthermore, -adrenoceptor activation stimulates the GTPase Rho and its effector Rho kinase (Carter et al. 2002; Crowley et al. 2002; Damron et al. 2002) which inhibits MLCP (Kimura et al. 1996), while NO has the opposite effect of inhibiting Rho/Rho kinase and activating MLCP (Sauzeau et al. 2000; Etter et al. 2001). Inhibition of Rho kinase has recently been shown to attenuate 2-adrenergic vasoconstriction (Carter et al. 2002), raising the possibility that reliance on this pathway could contribute to the enhanced susceptibility of 2-adrenoceptor responses to inhibition by NO.
In summary, the new findings of this study are that both 1- and 2-adrenoceptors can evoke constrictor responses in the microcirculation of slow-twitch muscle, and that the 2-adrenoceptor responses are particularly sensitive to inhibition by NO via a cGMP-dependent mechanism that requires KATP channel activation. Similar findings in fast-twitch muscle confirmed previous studies (Faber, 1988; Ohyanagi et al. 1992; Tateishi & Faber, 1995a; Thomas et al. 1997; Thomas & Victor, 1998), and suggested that skeletal muscle fibre type composition is not a determinant of the innate vascular responsiveness to -adrenoceptor activation. Based on these findings, we speculate that previously reported differences in vascular regulation in fast-twitch and slow-twitch muscles (Folkow & Halicka, 1968; Hilton et al. 1970; Gray, 1971; Thomas et al. 1994) are probably mediated by mechanisms upstream of the -adrenoceptors. These could include differences in the vascular innervation or activity of sympathetic nerves, in the densities or functional reserves of vascular -adrenoceptors, or in the local production and accumulation of muscle metabolites.
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References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1-adrenergic constriction than gastrocnemius arterioles. J Appl Physiol
92, 1808–1816.
Anderson
KM
&
Faber
JE (1991). Differential sensitivity of arteriolar 1- and 2-adrenoceptor constriction to metabolic inhibition during rat skeletal muscle contraction. Circ Res
69, 174–184.
Blatter LA & Wier WG (1994). Nitric oxide decreases [Ca2+]i in vascular smooth muscle by inhibition of the calcium current. Cell Calcium 15, 122–131.[CrossRef][Medline]
Bolotina VM, Najibi S, Palacino JJ, Pagano PJ & Cohen RA (1994). Nitric oxide directly activates calcium-dependent potassium channels in vascular smooth muscle. Nature 368, 850–853.[CrossRef][Medline]
Brayden JE (2002). Functional roles of KATP channels in vascular smooth muscle. Clin Exp Pharmacol Physiol 29, 312–316.[CrossRef][Medline]
Buckwalter
JB, Naik
JS, Valic
Z
&
Clifford
PS (2001). Exercise attenuates -adrenergic-receptor responsiveness in skeletal muscle vasculature. J Appl Physiol
90, 172–178.
Buckwalter
JB, Taylor
JC, Hamann
JJ
&
Clifford
PS (2004). Role of nitric oxide in exercise sympatholysis. J Appl Physiol
97, 417–423; Discussion 416.
Carter
RW, Begaye
M
&
Kanagy
NL (2002). Acute and chronic NOS inhibition enhances 2-adrenoreceptor-stimulated RhoA and Rho kinase in rat aorta. Am J Physiol Heart Circ Physiol
283, H1361–H1369.
Cornwell TL, Pryzwansky KB, Wyatt TA & Lincoln TM (1991). Regulation of sarcoplasmic reticulum protein phosphorylation by localized cyclic GMP-dependent protein kinase in vascular smooth muscle cells. Mol Pharmacol 40, 923–931.[Abstract]
Crowley
CM, Lee
CH, Gin
SA, Keep
AM, Cook
RC
&
Van Breemen
C (2002). The mechanism of excitation-contraction coupling in phenylephrine-stimulated human saphenous vein. Am J Physiol Heart Circ Physiol
283, H1271–H1281.
Damron
DS, Kanaya
N, Homma
Y, Kim
SO
&
Murray
PA (2002). Role of PKC, tyrosine kinases, and Rho kinase in alpha-adrenoreceptor-mediated PASM contraction. Am J Physiol Lung Cell Mol Physiol
283, L1051–L1064.
Dinenno
FA, Eisenach
JH, Dietz
NM
&
Joyner
MJ (2002). Post-junctional -adrenoceptors and basal limb vascular tone in healthy men. J Physiol
540, 1103–1110.
Etter
EF, Eto
M, Wardle
RL, Brautigan
DL
&
Murphy
RA (2001). Activation of myosin light chain phosphatase in intact arterial smooth muscle during nitric oxide-induced relaxation. J Biol Chem
276, 34681–34685.
Faber
JE (1988). In situ analysis of -adrenoceptors on arteriolar and venular smooth muscle in rat skeletal muscle microcirculation. Circ Res
62, 37–50.
Fleming BP, Gibbins IL, Morris JL & Gannon BJ (1989). Noradrenergic and peptidergic innervation of the extrinsic vessels and microcirculation of the rat cremaster muscle. Microvasc Res 38, 255–268.[CrossRef][Medline]
Folkow B & Halicka HD (1968). A comparison between ‘red’ and ‘white’ muscle with respect to blood supply, capillary surface area and oxygen uptake during rest and exercise. Microvasc Res 1, 1–14.[Medline]
Grange
RW, Isotani
E, Lau
KS, Kamm
KE, Huang
PL
&
Stull
JT (2001). Nitric oxide contributes to vascular smooth muscle relaxation in contracting fast-twitch muscles. Physiol Genomics
5, 35–44.
Gray
SD (1971). Responsiveness of the terminal vascular bed in fast and slow skeletal muscles to -adrenergic stimulation. Angiologica
8, 285–296.[Medline]
Guimaraes
S
&
Moura
D (2001). Vascular adrenoceptors: an update. Pharmacol Rev
53, 319–356.
Hilton
SM, Jeffries
MG
&
Vrbova
G (1970). Functional specializations of the vascular bed of soleus. J Physiol
206, 543–562.
Ikeoka
K
&
Faber
JE (1993). ANG II reverses selective inhibition of 2-adrenoceptor sensitivity after in vitro isolation of arterioles. Am J Physiol
265, H1988–H1995.[Medline]
Kamm KE & Stull JT (1985). The function of myosin and myosin light chain kinase phosphorylation in smooth muscle. Annu Rev Pharmacol Toxicol 25, 593–620.[CrossRef][Medline]
Keller
DM, Ogoh
S, Greene
S, Olivencia-Yurvati
A
&
Raven
PB (2004). Inhibition of KATP channel activity augments baroreflex-mediated vasoconstriction in exercising human skeletal muscle. J Physiol
561, 273–282.
Kimura K, Ito M, Amano M, Chihara K, Fukata Y, Nakafuku M, Yamamori B, Feng J, Nakano T, Okawa K, Iwamatsu A & Kaibuchi K (1996). Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase). Science 273, 245–248.[Abstract]
Lau KS, Grange RW, Chang WJ, Kamm KE, Sarelius I & Stull JT (1998). Skeletal muscle contractions stimulate cGMP formation and attenuate vascular smooth muscle myosin phosphorylation via nitric oxide. FEBS Lett 431, 71–74.[CrossRef][Medline]
McGillivray-Anderson
KM
&
Faber
JE (1991). Effect of reduced blood flow on 1- and 2-adrenoceptor constriction of rat skeletal muscle microvessels. Circ Res
69, 165–173.
Marshall
JM (1982). The influence of the sympathetic nervous system on individual vessels of the microcirculation of skeletal muscle of the rat. J Physiol
332, 169–186.
Murphy ME & Brayden JE (1995). Nitric oxide hyperpolarizes rabbit mesenteric arteries via ATP-sensitive potassium channels. J Physiol 486, 47–58.[Medline]
Ohyanagi
M, Faber
JE
&
Nishigaki
K (1991). Differential activation of 1- and 2-adrenoceptors on microvascular smooth muscle during sympathetic nerve stimulation. Circ Res
68, 232–244.
Ohyanagi
M, Nishigaki
K
&
Faber
JE (1992). Interaction between microvascular 1- and 2-adrenoceptors and endothelium-derived relaxing factor. Circ Res
71, 188–200.
Persechini
A, Kamm
KE
&
Stull
JT (1986). Different phosphorylated forms of myosin in contracting tracheal smooth muscle. J Biol Chem
261, 6293–6299.
Pfitzer
G (2001). Invited review: regulation of myosin phosphorylation in smooth muscle. J Appl Physiol
91, 497–503.
Robertson BE, Schubert R, Hescheler J & Nelson MT (1993). cGMP-dependent protein kinase activates Ca-activated K channels in cerebral artery smooth muscle cells. Am J Physiol 265, C299–C303.[Medline]
Rosenmeier
JB, Dinenno
FA, Fritzlar
SJ
&
Joyner
MJ (2003). 1- and 2-adrenergic vasoconstriction is blunted in contracting human muscle. J Physiol
547, 971–976.
Sauzeau
V, Le Jeune
H, Cario-Toumaniantz
C, Smolenski
A, Lohmann
SM, Bertoglio
J, Chardin
P, Pacaud
P
&
Loirand
G (2000). Cyclic GMP-dependent protein kinase signaling pathway inhibits RhoA-induced Ca2+ sensitization of contraction in vascular smooth muscle. J Biol Chem
275, 21722–21729.
Schlossmann J, Feil R & Hofmann F (2003). Signaling through NO and cGMP-dependent protein kinases. Ann Med 35, 21–27.[CrossRef][Medline]
Somlyo AP & Somlyo AV (1994). Signal transduction and regulation in smooth muscle. Nature 372, 231–236.[CrossRef][Medline]
Somlyo
AP
&
Somlyo
AV (2003). Ca2+ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase. Physiol Rev
83, 1325–1358.
Stull
JT, Gallagher
PJ, Herring
BP
&
Kamm
KE (1991). Vascular smooth muscle contractile elements. Cellular regulation. Hypertension
17, 723–732.
Tateishi
J
&
Faber
JE (1995a). ATP-sensitive K+ channels mediate 2D-adrenergic receptor contraction of arteriolar smooth muscle and reversal of contraction by hypoxia. Circ Res
76, 53–63.
Tateishi
J
&
Faber
JE (1995b). Inhibition of arteriole 2- but not 1-adrenoceptor constriction by acidosis and hypoxia in vitro. Am J Physiol
268, H2068–H2076.[Medline]
Thomas
GD, Hansen
J
&
Victor
RG (1994). Inhibition of 2-adrenergic vasoconstriction during contraction of glycolytic, not oxidative, rat hindlimb muscle. Am J Physiol
266, H920–H929.[Medline]
Thomas GD, Hansen J & Victor RG (1997). ATP-sensitive potassium channels mediate contraction-induced attenuation of sympathetic vasoconstriction in rat skeletal muscle. J Clin Invest 99, 2602–2609.[Medline]
Thomas
GD
&
Victor
RG (1998). Nitric oxide mediates contraction-induced attenuation of sympathetic vasoconstriction in rat skeletal muscle. J Physiol
506, 817–826.
Wray
DW, Fadel
PJ, Smith
ML, Raven
P
&
Sander
M (2004). Inhibition of -adrenergic vasoconstriction in exercising human thigh muscles. J Physiol
555, 545–563.
Wu CC, Chen SJ & Yen MH (1999). Cyclic GMP regulates cromakalim-induced relaxation in the rat aortic smooth muscle: role of cyclic GMP in KATP-channels. Life Sci 64, 2471–2478.[CrossRef][Medline]
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4 muscles per concentration.
